JPH0568446B2 - - Google Patents

Description

[Detailed description of the invention]

(1) Purpose of the Invention The present invention is an invention of a method for producing a soft capsule containing Bifidobacterium, which covers dried bacterial cells of Bifidobacterium with a film material. There have been many reports on the physiological significance of Bifidobacterium, which suppresses the growth of Escherichia coli, Clostridium perfringens, and Bacteroides, which are the bacteria that cause intestinal putrefaction, prevents diarrhea and constipation, and inhibits the growth of bacteria such as lactic acid and acetic acid. It is already widely known that it has excellent physiological effects such as producing organic acids and vitamins. However, Bifidobacterium powder generally has poor survivability and tends to lose activity. In addition, the texture was poor due to the odor peculiar to Bifidobacterium and the starch odor of the protective agent. Moreover, Bifidobacterium easily dies in acidic solutions, making it difficult to pass through the stomach at a pH of 1.2 to 5.0 and reach the intestines while maintaining its activity. The inventors of the present application have invented a method for producing Bifidobacterium soft capsules that overcome these drawbacks of Bifidobacterium powder, are highly palatable without the unpleasant odor peculiar to Bifidobacteria, and can survive stably for a long period of time. . Furthermore, by the production method of the present invention, it is possible to produce soft capsules containing Bifidobacterium, in which the Bifidobacteria do not die in the stomach after drinking, and can reach the intestines alive, and the capsules dissolve in the intestines. Ta. (2) Structure of the Invention The present invention solves the above-mentioned problems that the conventional Bifidobacterium powder had, and it is made by adding a protective agent to the Bifidobacterium powder, which has a melting point of 30 to 45°C and a melting point width of 3. Capsule core liquid suspended in hardened oil below ℃ and a coating liquid made by adding pectin and/or sodium alginate to gelatin are dropped into cooled oil to form capsules, and then immersed in calcium salt solution. The present invention provides a method for producing soft capsules containing Bifidobacteria, characterized by the following. The Bifidobacterium used in the present invention is a normal Bifidobacterium (genus Bifidobacterium), and any Bifidobacterium belonging to this group can be used. The major ones are Bifidobacterium longum, Bifidobacterium infantis, and Bifidobacterium adolescentes.
adolescentis), Bifidobacterium breve, etc. A protective agent is added to the Bifidobacterium powder, and it is desirable to use, for example, starch, especially dry starch. The protective agent is added before freeze-drying the Bifidobacterium, but may be added after freeze-drying to reduce the water activity to 0.2 or less. Bifidobacterium powder added with a protective agent is added to the melting point.
Suspend in hydrogenated oil with a melting point range of 3°C or less at 30-45°C and use this as a core liquid. By using hydrogenated oil with a narrow melting point range,
The suspension can solidify immediately. This prevents the moisture in the coating solution from moving into the suspension, and can increase the survival rate of Bifidobacterium. The amount of Bifidobacterium powder is based on the amount of hydrogenated oil used.
It is 30% or less, preferably 25% or less. Bifidobacterium powder and fat are mixed at a temperature 2 to 5°C higher than the melting point of the fat. On the other hand, a gelatin solution is used as the coating solution. The solid content of the gelatin solution is preferably 20 to 35%, and pectin is added to the gelatin, or sodium alginate is added together with or in place of pectin. The amount of pectin added is preferably 5 to 20% of the amount of gelatin. Known methods can be used to form capsules. For example, double pipe nozzle (Special Publication No. 51-8875
No.), the coating liquid is poured into the outer tube nozzle and the core liquid is poured into the inner tube nozzle, and the gelatin is solidified by dropping it into the cooled oil, forming a capsule.
Next, the oil used for cooling is removed from the capsule,
dry. Further, the film is entericized by immersing it in a calcium solution according to the method described in JP-A-58-172313, and after being taken out, it is dried so that the moisture content of the film is 8 to 15%. Pectin reacts with calcium and coagulates, forming an acid-stable film. As a result, soft capsules containing Bifidobacterium were obtained. This capsule passed the enteric coating test based on the disintegration test method of the Japanese Pharmacopoeia, and was found to dissolve in the intestines but not in the stomach. (3) Example 1 80 parts of hydrogenated oil (melting point range 33-35°C, iodine value 2 or less) mainly made from coconut oil and palm kernel oil was kept at 38°C, and lyophilized bifid bacteria was added to it. A mixture of 1 part of Bifidobacterium longum and 9 parts of dried potato starch (water activity 0.15).
20 parts were suspended and used as a nuclear solution. On the other hand, the coating liquid contains 75 parts of gelatin and 5 parts of glycerin.
1 part pectin and 10 parts pectin, and the solid content was adjusted to 28%, and dissolved in hot water at 38°C. Using a double tube nozzle, apply the coating liquid to the outer tube.
The core fluid was passed through the inner tube and dropped into cooled oil (vegetable oil, etc.) to obtain soft capsules containing bifidobacteria with an average diameter of 6 mm. Next, the capsules were immersed in a 5% calcium chloride solution for enteric treatment, taken out, and dried with cold air. This resulted in capsules with a film moisture content of 11%. Bifidobacterium longum lived in this capsule at a rate of 7.3×10 ⁷ cells/g. Example 2 Bifidobacterium breve was used as the freeze-dried bacterial cell, and the coating liquid was composed of 70 parts of gelatin, 5 parts of D-sorbitol, and 12 parts of sodium alginate, and the solid content was 25%.
Bifidobacterium-containing soft capsules with an average diameter of 6 mm were obtained using a double tube nozzle and prepared in the same manner as in Example 1, except that the capsules were prepared as follows. In this capsule, 7.0×10 ⁷ cells/g of Bifidobacterium breve were alive. (4) Survival Experiment A survival experiment was conducted on the soft capsules produced in Example 1 above. As a result, it was found that even after 6 months, the number of Bifidobacterium bacteria in the capsule decreased only slightly, indicating extremely high survivability.

[Table] (5) Disintegration test A disintegration test was conducted on the soft capsules produced according to the above example. The disintegration test was conducted based on the test method listed in the Japanese Pharmacopoeia, 10th revision, ``Disintegration test method (6) Enteric-coated preparations, 1. Preparations other than granules and capsules filled in granule form.'' . The first liquid (PH1.2) is made by adding 24.0 ml of dilute hydrochloric acid and water to 2.0 g of sodium chloride to make 1000 ml.
A second solution (PH6.8) was prepared by adding 118 ml of 0.2N sodium hydroxide test solution and water to 250 ml of 0.2M potassium dihydrogen phosphate test solution to make 1000 ml. The soft capsules showed no abnormalities in the first liquid even after 120 minutes, and completely dissolved in the second liquid after 10 minutes. As a result, the soft capsules met and passed the enteric coating test based on the disintegration test method of the Japanese Pharmacopoeia. (6) Effects Bifidobacterium-containing soft capsules can be produced by the production method of the present invention. As a result, palatability could be improved without making the user feel the unpleasant odor peculiar to Bifidobacterium or the starch odor of the protective agent. Furthermore, the soft capsules produced by the method of the present invention were able to survive stably for a long period of time, and the survival rate of Bifidobacterium in the capsules was extremely high. Furthermore, by the method of the present invention, it was possible to produce a soft capsule containing Bifidobacterium in which the Bifidobacterium does not die in the stomach and reaches the intestines alive.

Claims (1)

[Claims] 1. Capsule core liquid prepared by adding a protective agent to freeze-dried Bifidobacterium powder, suspending it in hydrogenated oil with a melting point of 30 to 45°C and a melting point width of 3°C or less, and gelatin with pectin and/or alginic acid. A method for producing soft capsules containing Bifidobacterium, which comprises dropping a sodium-added coating liquid into cooled oil to form capsules, and then immersing the capsules in a calcium salt solution. 2. The method for producing soft capsules containing Bifidobacterium according to claim 1, which uses starch as a protective agent. 3. The method for producing soft capsules containing Bifidobacterium according to claim 1, wherein a protective agent is added before freeze-drying the Bifidobacteria. 4. The method for producing soft capsules containing Bifidobacterium according to Claim 1, wherein the protective agent is added after freeze-drying the Bifidobacteria at a water activity of 0.2 or less. 5. The method for producing soft capsules containing Bifidobacterium according to claim 1, wherein the solid content of the gelatin film liquid is 20 to 35%. 6. The method for producing a soft capsule containing Bifidobacterium according to claim 1, wherein the pectin added to the gelatin coating liquid is 5 to 20% of the amount of gelatin.